Active surface transport of metabotropic glutamate receptors through binding to microtubules and actin flow

Active surface transport of metabotropic glutamate receptors through binding to microtubules and actin flow
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通过与微管和肌动蛋白流结合进行代谢型谷氨酸受体的主动表面转运

DOI:
10.1242/jcs.00822
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发表时间:
2003
影响因子:
4
通讯作者:
D. Choquet
D. Choquet
中科院分区:
生物学2区
文献类型:
--
作者:
Arnauld Sergé;L. Fourgeaud;A. Hémar;D. Choquet

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神经递质受体通过与支架蛋白和细胞骨架元件的相互作用集中并稳定在给定位点,例如突触。受体的转运首先涉及细胞内储存的受体的定向囊泡运输,然后将其靶向质膜。一旦在细胞表面表达,受体被认为通过质膜平面中的随机布朗扩散到达其最终位置。在这里,我们研究代谢型谷氨酸受体 mGluR5 是否也可以在细胞表面主动转运。我们使用单粒子追踪技术实时追踪 mGluR5 在神经元生长锥或成纤维细胞片状伪足表面的运动,这两者都具有特别活跃的细胞骨架。我们发现,经过一定的滞后时间后,mGluR5 会进行定向向后运输,这取决于肌动蛋白流。在肌动蛋白解聚时,定向运动被抑制,但受体仍然与刚性结构结合。相比之下,受体转运和固定被微管解聚完全抑制,但微管稳定有利于受体转运和固定。此外,mGluR5 可以与来自大鼠大脑的微管蛋白进行免疫沉淀,证实 mGluR5 与微管结合的能力。我们提出 mGluR5 可以通过肌动蛋白介导的微管逆行运输在细胞表面运输。这一过程可能在突触形成过程中或谷氨酸介导的生长锥趋化过程中的受体靶向和组织中发挥作用。
Receptors for neurotransmitters are concentrated and stabilized at given sites such as synapses through interactions with scaffolding proteins and cytoskeletal elements. The transport of receptors first involves directed vesicular trafficking of intracellularly stored receptors followed by their targeting to the plasma membrane. Once expressed at the cell surface, receptors are thought to reach their final location by random Brownian diffusion in the plasma membrane plane. Here, we investigate whether the metabotropic glutamate receptor mGluR5 can also be transported actively on the cell surface. We used single particle tracking to follow mGluR5 movement in real time at the surface of neuronal growth cones or fibroblast lamellipodia, both of which bear a particularly active cytoskeleton. We found that after a certain lag time mGluR5 undergoes directed rearward transport, which depends on actin flow. On actin depolymerization, directed movement was suppressed, but receptors still bound to a rigid structure. By contrast, receptor transport and immobilization was fully suppressed by microtubule depolymerization but favored by microtubule stabilization. Furthermore, mGluR5 could be immunoprecipitated with tubulin from rat brains, confirming the ability of mGluR5 to bind to microtubules. We propose that mGluR5 can be transported on the cell surface through actin-mediated retrograde transport of microtubules. This process may play a role in receptor targeting and organization during synapse formation or during glutamate-mediated growth cone chemotaxis.
一种与神经元生长锥中定点肌动蛋白丝组装相关的海兔细胞粘附分子。
DOI: 10.1242/jcs.109.12.2843
发表时间: 1996
影响因子: 4
作者:
Thompson,C;Lin,CH;Forscher,P
通讯作者: Forscher,P
神经生长因子刺激β1整合素与生长锥丝状伪足中不同运输机制的偶联。
DOI: 10.1242/jcs.113.17.3003
发表时间: 2000
影响因子: 4
作者:
Grabham,PW;Foley,M;Umeojiako,A;Goldberg,DJ
通讯作者: Goldberg,DJ